Hemostasis-thrombosis and shock

edema

* accumulation of vascular fluid
* fluid balance across capillary wall is in homeostasis

homeostasis

no net fluid loss or gain

edema occurs due to

* increased hydrostatic P
* Decreased plasma oncotic

lymphatics

normally carry away only small amount of fluid

* serve as a backup system to remove excess tissue

example of increased hydrostatic P

hypertension

example of decreased plasma oncotic P

renal disease (nephrotic syndrome)

Categories of edema

* increase hydrostatic pressure
* decrease plasma oncotic P
* lymphatic obstruction
* Na-retention
* inflammation

increased hydrostatic pressure

* CHF, pericarditis, ascites
* thrombosis
* LE inactivity, venous hypertension

decrease plasma oncotic P

liver and kidney dx, malnutrition

lymphatic obstruction

post Sx and rad Tx, metastasis dx

Na-retention

kidney dx, HTN, excess Na

where fluid accumulates

* pericardium
* pleural space
* peritoneum
* lower extremities
* anasarca: serve, generalized edema
* locally at site of inflammation

pitting edema

* pressure with finger leaves indentation
* pressure over bony prominence

subcutaneous edema

edema in tissue planes, gravity dependent

transudate

* fluid w/ low protein
* associated w/ hydrodynamic derangement and protein loss (CHF, renal disease)
* thin watery fluid
* blisters

exudate

* high protein content, specific gravity > 1.02
* inflammation, increase vascular permeability (wound drainage)
* acne

preortibal edema

* swelling of eye lid
* loose connective tissue around eye prone to swelling

edema and heart failure

heart failure is associated with increased hydrostatic P, multi system dysfunction and translate accumulation in a variety of locations

R - sided HF

* systemic edema
* ankles, pre-orbital

L-sides HF

* pulmonary edema
* fluid accumulation in alveoli

manifestation of pulmonary edema

* rales (crackles)
* shortness of breath
* orthopnea
* decrease exercise tolerance

manifestation of cerebral edema

* swelling of a confined space results in increase P
* confusion
* decrease alertness and cognitive functioning
* coma
* death

swelling of a confined space results in increased pressure

* herniation of brain stem and/or midline shift
* damage to nerve cell bodies and axons

manifestation of subcutaneous edema

* impairs wound healing
* risk of DVT

hyperemia

* active process of increased blood flow due to vasodilation
* burse or laceration
* red, swollen, painful, inflamed

congestion

* passive process of decreased venous blood flow and back up of fluid
* liver disease with ascites
* bluish, cyanosis, chronic in nature
* in lung
* chronic changes
* thickening of alveolar septa
* fibrosis
* infiltration of WBCs

hyperemia and congestion

local increase in blood volume

hematoma

bleed into enclosed space

petechiae

diffuse, minute (1 mm) bled into tissue

* associated with thrombocytopenia (low platelet count)

purprua

* 3 -5 mm hemorrhage
* associated with thrombocytopenia and vasculitis

ecchymosis

subcutaneous bruising

accumulations of blood in body cavities

* hemothorax
* hemopericardium
* hemarthrosis

hemostasis

delicate balance btw clot free circulating blood and rapid formation of a thrombus during hemorrhage

homeostasis depends on 3 systems

* vascular wall
* platelets
* coagulation cascade

hemostatic process

* initial injury
* smooth muscle response
* endothelial cell response

initial injury

* endothelial cell damage
* exposure of ex cell matrix - tissue factor

smooth muscle response

local vasoconstriction

endothelial cell response

* von Willebrand factor (vWF)
* platelets adhere to ECM
* shape change
* granule release
* ADP release
* thromboxane A2
* primary hemostatic plug (initial thrombus)

2 degree plug and counter-thrombosis

* local activation of coagulation cascade
* fibrin polymerization
* counter-thrombosis mechanisms

local activation of coagulation cascade

* tissue factor (activates extrinsic coagulation pathway)
* platelet phospholipids

fibrin polymerization

cements the clot forming 2degree plug

count-thrombosis mechanisms

* tissue plasminogen activator (TPA)
* thrombomodulin

coagulation cascade

* platelet factors interact w/ other coagulation elements to form the cascade
* series of conversions leading to thrombin
* 3 components for each Rx
* occurs on platelet surface (lipid membrane)
* Ca play role in binding factors
* stays localized

3 components for each Rx

* enzyme
* substrate
* cofactor

enzyme

activated factor

substrate

pro-enzyme factor

co-factor

accelerators

thrombin

* key, multi-dimensional role
* catalyzes the conversion of fibrinogen to fibrin final step in clot
* requires GpIIb-IIIa receptor

intrinsic pathway

* everything needed is already present in blood
* in vitro phenomena
* connection btw pathways

extrinsic pathway

* requires factors outside of the blood
* activated by tissue factor produced with injury
* activates components of intrinsic pathway

pro-enzymes

red

active enzymes

green

the two pathways come together at

factor X

activated thrombin actives

* multiple signals
* inflammation
* anticoagulation (limits clot locally)

fibrinolytic system

* anti thrombin
* protein C & S
* plasmin

anti-thrombin

* inhibit activity of thrombin
* activated by binding to heparin like molecule

Proteins C & S

vitamin K-dependent proteins that inactivate factors Va and VIIIa

plasmin

* activated by tissue plasminogen activator (t-PA)
* part of the fibrinolytic system that degrades fibrin

dominant factor of thrombosis

endothelial injury

additional factors thrombosis

* altered blood flow
* laminar vs turbulence
* stasis
* aneurysm
* hypercoagulability
* primary syndromes
* secondary syndromes

thrombosis is known as

Virchow’s triad

primary causes of thrombosis

* factor V mutation
* anti-thrombin deficiency
* protein C and S deficiency

secondary causes of thrombosis

* bed rest, immobilization
* tissue damage (MI, surgery)
* cancer, paralysis
* DIC, heparin-induced thrombocytopenia HIT

lower risk for thrombosis

* A-fib
* sick cell dx


* smoking

fate of a thrombosis

* propagation
* embolization
* dissolution
* organization and re-canalization

propagation

* antero or retro grade
* obstruct larger vessel

dissolution

fibrinolytic system breaks it down

atherosclerosis

ischemic heart disease is a multi-system disease

fatty streaks of atherosclerosis

* begin in 2nd or 3rd decade
* oxidation of LDL

inflammation & infection of atherosclerosis

* oxidation of LDL
* pro-atheroma
* cytokines
* promotes leukocytes
* local versus distal infection
* DM, dental caries
* liver acute phase reaction
* C reactive protein and cytokines

hypertension

* damage to endothelial cells
* atherosclerosis

plaque formation: atherosclerosis

* maturity
* thrombosis and embolism

systemic acute phase response

* over all body response to stress
* fever
* malaise
* somnolence
* skeletal m. breakdown
* hypotension
* hepatic production of A-P proteins

hepatic production of A-P proteins

* cytokines IL-1, IL-6, TNF-alpha
* produce fever and other negative effects via prostaglandins

mediators of acute-phase response directly contribute to

* atherosclerosis
* induction of adhesion molecules on endothelial cells
* activation of immune cells

biomarkers of inflammation

* C-reactive protein (CPR)
* interleukin 6
* tumor necrosis factor-alpha

CPR

* best clinical predictor
* primarily produced in liver, acts throughout body

TNF-alpha

involved with other disease including CA and HF

conditions predisposing to low level inflammation

* usual risk factors for HD
* LDL, HTN, smoking
* obesity
* DM
* increased body mass index

thromboembolism

* 99% of all emboli
* coronary
* pulmonary
* cerebral
* air
* fat
* amniotic fluid

coronary thromboembolism

* CP
* SOB
* sweating
* LOC
* dizziness
* N & V

pulmonary thromboembolism

* majority are silent
* SOB
* CP
* LOC
* cyanosis

cerebral thromboembolism

* slurred speech
* diorientation
* LOC
* difficulty walking


* dizziness

air thromboembolism

2 degrees to IV access problem/ BENDS or obstetric procedures

fat thromboembolism

2 degrees to long bone fracture

infarction

* area of ischemia resulting from occlusion of flow
* typically wedge shaped
* reflecting vascular bed
* ischemic coagulative necrosis
* most infracts replaced by scare tissue, except brain

red infarcts

* involves hemorrhage
* venous infarcts
* ovaries, testes
* lung small intestines
* tissue w/ minimal structure of dual circulation
* when flow is re-established

white infarcts

* complete loss of blood
* arterial occlusions in organs such as spleen, heart, kidney

shock

* cardiovascular collapse
* final common pathway for many conditions
* system hypo-profusion secondary

shock is final common pathway for

* trauma
* hemorrhage
* burns
* large MI
* PE
* GI infarction
* infections --- sepsis

system hypo-perfusion secondary to

* decreased CO
* reduced circulating volume

What are the three major types of shock

* cardiogenic
* hypovolemic
* septic

clinical example of cardiogenic shock

* MI
* PE
* ventricular rupture
* arrhythmia
* tamponade

mechanism of cardiogenic shock

pump failure secondary to myocardial damage, obstruction or extrinsic pressure

clinical example of hypovolemic shock

* hemorrhage
* fluid loss (vomiting, diarrhea, burns)

mechanism of hypovolemic shock

inadequate blood volume

clinical example of septic shock

* overwhelming microbial infection
* endotoxin
* bacterial septicemia
* fingal sepsis

mechanism of septic shock

* peripheral vasodilation
* pooling
* endothelial injury
* leukocyte activation & DIC

septic shock

* 25 to 50% mortality rate
* primary cause of death in ICU patients
* most caused by gram - bacilli and fungi

gram - bacilli and fungi

* endotoxin
* bacterial wall lipopolysacharide
* LPS has toxic fatty acid core and sugar coating
* massive monocyte, macrophage, and neutrophil activation
* cytokine production
* activation of complement